Over the past 17 years, we have collaborated with the Harvard School of Public Health to study HIV infections in Senegal. We have developed our clinical and virologic research capacity to support the national ARV program in Senegal, now in effect since 1998. The proposed research, infrastructure development and training will not only support the National ARV program in Senegal, but provide important new data on treatment regimens applicable to the African setting. 1) Clinical trials of ARV therapy - Senegal was one of the first African nations to initiate a national ARV program, now with 3-4 years of experience and two completed clinical trials. We propose to continue this effort with new pilot phase II trials to evaluate the safety and efficacy of a relatively new triple nucleoside reverse transcriptase inhibitor (NRTI) regime for first line treatment of HIV-1, HIV-2 and dual infections. Alternative regimens are also proposed that may provide the basis for subsequent comparison trials and development of a sequence of efficacious regimes that may be amenable to long-term treatment of HIV infection. Research studies proposed within the context of the ARV trial will seek to characterize the wild type reverse transcriptase and protease genes and characterize the dynamics of drug resistant mutations that occur under drug pressure and clinical failure. Other studies will determine the viral dynamics of HIV-2 infection under potent ARV therapy and compare these to our understanding of HIV-1 subtype B infection dynamics. 2) Infrastructure development - We will establish and strengthen collaborations with clinicians involved in ARV therapy to develop methods of clinical management to enhance adherence to therapeutic regimes, and provide experience in clinical trials of ARV. We will develop and augment our clinical immunology and virology capabilities to better support the clinical management of HIV patients on ARV therapy. This will include FACs based immunologic assays and quantitative DNA and RNA PCR assays for HIV-1 and HIV-2. Through collaboration with Boston, we will develop HIV sequencing capabilities for our laboratories. This will allow for the identification of ARV resistant viruses through in vitro as well as sequence techniques. 3) Training for larger scale ARV programs. This multidisciplinary program will require many well Trained personnel. We will propose several workshops and training fellowships that will allow investigators from other parts of Senegal and West Africa to come to our laboratories to train in ARV therapy programs. This will include both clinical management and laboratory methods and practices required for effective ARV management.